This application for a Center for Excellence in Research on Complementary and Alternative Medicine (CERC) at the Osher Center for Integrative Medicine at the University of California - San Francisco brings together a strong multidisciplinary team of scientists to rigorously study the efficacy of a mind-body meditation-based intervention, Mindfulness Based Stress Reduction (MBSR), in people with early stage HIV disease (CD4+ T cells > 350/mu l) to slow disease progression and extend the period during which antiretroviral treatment (ART) is not indicated. Currently there are no prescribed treatments for this stage of HIV. Three closely integrated studies are planned: Project 1 is a randomized clinical trial to determine whether MBSR decreases the rate of decline of CD4+ T cells and lowers HIV RNA levels in HIV+ persons with early stage HIV disease who are not receiving ART, compared to a control group. Additional outcomes include quality of life and depression. Participants (N=330) will be followed for one year; 165 will be assigned to the MBSR group and 165 to the control group. Proiect 2 will determine the effects of MBSR on stress processes, including the appraisal of stress, negative and positive affect, and biological stress arousal, including basal anabolic (DHEA, testosterone) and catabolic (cortisol, cathecholamines) responses to the stress of daily life (Study A), and anabolic and catabolic responses and autonomic nervous system reactivity to a controlled laboratory stressor (Study B). In addition to providing findings about generic biological effects of MBSR on the stress process, Project 2 will provide information regarding neuroendocrine pathways through which MBSR might also affect immune functions that are studied in Project 3. Project 3 will test postulated immune pathways through which stress and MBSR affect HIV replication and immune functioning, including CCR5 and CXR4 density (co-receptors for HIV cell entry of CD4 T-cells), T-cell activation, levels of cytokines that are important in immune responses that may be influenced by stress, and NK and plasmacytoid dendritic cell numbers and function. Two cores will support the research projects. The Administrative Core provides scientific leadership including the Scientific Advisory Committee and the Executive Committee and. fiscal, personnel, and space administration. The Methods Core provides statistical support, data management services, and specimen banking for the CERC projects. The synergy and fertile environment provided by the CERC structure will lead to new and supplemental research on efficacy and mechanisms of actions of mind-body approaches to patient care.